We propose to test several theories as to the pathogenesis of Graves' hyperthyroidism, the nature of euthyroid Graves' ophthalmopathy and the underlying etiology of Graves' disease. Some aspects of its relationship to Hashimoto's disease will also be examined. The design is to study many indicators of pituitary-thyroid function in parallel with assays for serum thyroid-stimulating immunoglobulins in groups of patients in whom the disease may be evolving. The groups include euthyroid first-degree relatives of patients with Graves' and Hashimoto's diseases, patients with hyperthyroidism during and after treatment with propylthiouracil, and patients with euthyroid Graves' ophthalmopathy. The test battery will include assays of LATS, LATS-protector, TSH-displacing IgG, thyroid adenylate stimulating IgG, antithyroglobulin, antimicrosomal antibody, free T4, free T3, TRH response test, T3 suppression test and HLA typing. In addition, in vitro studies are planned to examine the interactions of LATS, LATS-protector and TSH with the TSH-receptor in thyroid membranes. LATS-protector and TSH-displacing activity will be compared to each other as estimates of thyroid-stimulating immunoglobulin level in Graves' patients. Studies will be conducted to determine if some anti TSH-receptor antibodies are inhibitory, although most seem to be stimulatory.